1. Field of the Invention (Technical Field)
The present invention relates to materials, methods and processes for making a hydrophilic and lubricious coating, wherein a hydrophilic polymeric unit is cross-linked by means of a plasma process with a double bond monomer, wherein the coating optionally further includes a bifunctional spacer to which the hydrophilic polymeric unit is bound. Also provided is the hydrophilic and lubricious coating and medical devices including the coating.
2. Background Art
Note that the following discussion refers to a number of publications by author(s) and year of publication, and that due to recent publication dates certain publications are not to be considered as prior art vis-a-vis the present invention. Discussion of such publications herein is given for more complete background and is not to be construed as an admission that such publications are prior art for patentability determination purposes.
For many medical devices, it is preferable if a coating or other contacting surface has several properties, including biocompatibility and lubricity. Device surfaces and coatings that are water absorbent and lubricious may be effectively employed with, for example, stents, screws, tubing, catheters, wire guides, needles, sutures, and the like. Coatings that are hydrophilic and lubricious can be contacted with tissues with decreased trauma. For example, any medical device, such as a bandage, suture, tubing, catheter, guide wire and the like, may be more conveniently removed with less trauma to associated tissue if the surface is lubricious.
Similarly, it is a requirement for medical device surfaces that the surface or other coating be biocompatible. Any implantable medical device requires biocompatibility, in order to avoid adverse reactions. In normal application, such devices are expected to function in intimate contact with living tissue and blood. This contact requires a delicate balance between ensuring that the device can function in the complex extra- and intra-cellular environment and maintaining the living tissues and blood.
Lubricity is, in part, related to biocompatibility and thromboresistance, particularly since the degree of lubricity of a coating is related to wear of the coating due to contact with other surfaces. For devices, such as needles, sutures, catheters and the like, that transit tissue or abrasive substrates, a high degree of lubricity is desired, concomitant with biocompatibility and a high degree of wear resistance. Thus coatings that are lubricious, but are not resistant to contact with tissue or abrasive substrates, do not function well in medical devices.
Long-term use of most polymeric substrates frequently results in mechanical failure, the promotion of blood clot formation, or physical degradation due to unfavorable interactions with tissue or blood environments. Thus it is desirable to have coatings or other composites for polymeric substrates that are hydrophilic and lubricious, provide superior strength, do not promote blood clot formation, and which do not interact with the tissue or blood environment. The specific requirements of each device vary depending on the degree and duration of contact and the nature of the application.
Cross-linking of polymers to form a lubricious surface has been explored. For example, International Patent Application WO 02/053664, entitled Absorbent, Lubricious Coating and Articles Coated Therewith, discloses a coating consisting of a cross-linked hydrogel copolymer including water soluble base polymers with graft polymerized organic moieties that react with water to form a silanol group, wherein the copolymer is cross-linked through the silanol groups. However, in this coating and method the crosslinking is solely through the silane groups, forming an Sixe2x80x94Oxe2x80x94Si cross-link. U.S. patent Application No. 2002/0049281, Process for Cross-Linking Hyaluronic Acid to Polymers, discloses a method for double crosslinking of hyaluronic acid derivatives, presumably with one bond formed by cross-linking via hydroxyl groups and the other via, for example, carboxyl groups. However, this method requires lengthy reactions, up to forty-eight hours, and extreme pH changes, ranging from less than pH 4 to pH 12. U.S. Pat. No. 6,169,127, entitled Plasma-Induced Polymer Coatings, discloses coatings for contact lenses utilizing after-glow plasma-induced polymerization of an unsaturated monomeric compound, with cross-linking by concurrent after-glow plasma-induced polymerization of two monomers, such as a primary monomeric vinyl compound and a cross-linking agent. This method requires co-polymerization of the two monomers, and does not permit prior application of a monomer or polymeric unit to be subsequently cross-linked or chemical complexation of a monomer or polymeric unit to a linking moiety with the crosslinking subsequent to such complexation.
Prior art coatings employing plasma polymerization are known in the art. These include the coatings and methods disclosed in U.S. Pat. No. 5,463,010, to Hu, et al., entitled Hydrocyclosiloxane Membrane Prepared By Plasma Polymerization Process; and U.S. Pat. No. 5,650,234, to Dolence et al., entitled Electrophilic Polyethylene Oxides for the Modification of Polysaccharides, Polypeptides (Proteins) and Surfaces. However, these methods do not disclose plasma crosslinking utilizing a polymerizable hydrophilic polymeric unit in conjunction with a plasma consisting of a double bond monomer.
None of the preceding references disclose coatings or methods wherein base hydrophilic polymeric units applied by conventional means, such as dipping, are subsequently cross-linked by plasma polymerization of a monomer, such as a double bond monomer, resulting in a hydrophilic and lubricious coating.
In one embodiment the invention provides a plasma cross-linked hydrophilic and lubricious coating wherein a hydrophilic polymeric unit is cross-linked in situ with a plasma deposited double bond monomer. The hydrophilic polymeric unit can be an ethylene oxide with one or more primary or secondary alcohol groups, including in a preferred embodiment 2,2xe2x80x2[(methylethylidine)-bis(4,1-phenyleneoxymethylene)]-bis-oxirane-polymer (PEOC). Alternatively, the hydrophilic polymeric unit can be a glycosaminoglycan, including a long chain linear polysaccharide such as hyaluronic acid, hyaluronan, dextran, cellulose or methyl cellulose. Preferably the double bond monomer includes a Cxe2x95x90C, Cxe2x95x90N or Cxe2x95x90O double bond, and in a preferred embodiment is N-trimethylsilyl-allylamine (TMSAA), ethylene, propylene or allyl alcohol. The coating can also include a bifunctional spacer covalently bonded to at least a portion of the hydrophilic polymeric unit. In a preferred embodiment, the bifunctional spacer is xcex1-hydro-xcfx89-hydroxypoly(oxy-1,2-ethanediyl)-bis-(1-hydroxbenzotriazolyl carbonate) (HPEOC). The coating can also include a reactive group, such as a primary or secondary amine, covalently bonded to the bifunctional spacer. In one embodiment, the hydrophilic polymeric unit and the bifunctional spacer are cross-linked with the plasma deposited double bond monomer.
The invention further includes a medical device for insertion into the body of a mammal, which medical device has at least one contacting surface for contacting bodily fluids or tissues, wherein the contacting surface has a coating of this invention. The contacting surface may include a metallic or polymeric material. The medical device may be a stent, catheter, shunt, valve, pacemaker, pulse generator, cardiac defibrillator, spinal stimulator, brain stimulator, sacral nerve stimulator, lead, inducer, sensor, seed, screw, anchor, anti-adhesion sheet, suture, needle, lens, joint or, in general, any implantable medical device known or hereafter developed.
The invention further includes a method for coating a surface with a hydrophilic and lubricious coating composition, the method including the steps of contacting a hydrophilic polymeric unit to the surface to be coated and cross-linking the hydrophilic polymeric unit by plasma deposition of a double bond monomer. The method may optionally include the additional steps of introducing a reactive group to the surface and contacting a bifunctional spacer with the reactive group under conditions whereby the bifunctional spacer is covalently bonded to the reactive group, it being understood that the hydrophilic polymeric unit is contacted to the surface to be coated with the bifunctional spacer under conditions whereby the hydrophilic polymeric unit is covalently bonded to the bifunctional spacer. The plasma employed is conventionally a radiofrequency plasma. In a preferred embodiment the plasma deposition is for at least five minutes, and preferably for at least ten minutes. The reactive group may be a primary amine or secondary amine, and if a secondary amine, may include plasma deposition of TMSAA. A primary object of the present invention is to provide a method to cross-link a polymeric unit coating by plasma deposition of a double bond monomer, such that a cross-linked lubricious coating results.
Another object of the present invention is to provide a coating that is both biocompatible and lubricious, including hydrophilic polymeric units cross-linked by means of a plasma deposited double bond monomer.
Another object of the present invention is to provide a coating with increased wear and resistance characteristics, resulting from plasma crosslinking utilizing a double bond monomer.
Another object of the present invention is to provide a coating wherein characteristics, including lubricity and wear resistance, may be altered by varying the plasma deposition time or plasma energy, or both, of the double bond monomer plasma.
Another object of the present invention is to provide a method for crosslinking a hydrophilic polymer that does not require pH adjustments, lengthy reaction times or chemical reaction solutions.
Another object of the present invention is to provide a coating including a bifunctional spacer covalently bonded to a reactive group anchored on a substrate surface, wherein the bifunctional spacers are cross-linked to hydrophilic polymeric units by means of plasma deposited double bond monomers.
Another object of the present invention is to provide a hydrophilic and lubricious cross-linked centeral that may be applied to any substrate, including metal, polymeric and ceramic substrates.
Other objects, advantages and novel features, and further scope of applicability of the present invention will be set forth in part in the detailed description to follow, taken in conjunction with the accompanying drawings, and in part will become apparent to those skilled in the art upon examination of the following, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.